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Neurochemistry International Oct 2016Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids... (Review)
Review
Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication.
Topics: Animals; Brain; Butyrates; Dairy Products; Energy Metabolism; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans
PubMed: 27346602
DOI: 10.1016/j.neuint.2016.06.011 -
F1000Research 2021Coronavirus disease 2019 (CoVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has affected more than 100 million lives. Severe CoVID-19 infection may... (Review)
Review
Coronavirus disease 2019 (CoVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has affected more than 100 million lives. Severe CoVID-19 infection may lead to acute respiratory distress syndrome and death of the patient, and is associated with hyperinflammation and cytokine storm. The broad spectrum immunosuppressant corticosteroid, dexamethasone, is being used to manage the cytokine storm and hyperinflammation in CoVID-19 patients. However, the extensive use of corticosteroids leads to serious adverse events and disruption of the gut-lung axis. Various micronutrients and probiotic supplementations are known to aid in the reduction of hyperinflammation and restoration of gut microbiota. The attenuation of the deleterious immune response and hyperinflammation could be mediated by short chain fatty acids produced by the gut microbiota. Butyric acid, the most extensively studied short chain fatty acid, is known for its anti-inflammatory properties. Additionally, butyric acid has been shown to ameliorate hyperinflammation and reduce oxidative stress in various pathologies, including respiratory viral infections. In this review, the potential anti-inflammatory effects of butyric acid that aid in cytokine storm depletion, and its usefulness in effective management of critical illness related to CoVID-19 have been discussed.
Topics: Butyrates; Dexamethasone; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34046165
DOI: 10.12688/f1000research.51786.1 -
Neurochemistry International Jun 2024Maintaining an optimum microbial community within the gastrointestinal tract is intricately linked to human metabolic, immune and brain health. Disturbance to these... (Review)
Review
Maintaining an optimum microbial community within the gastrointestinal tract is intricately linked to human metabolic, immune and brain health. Disturbance to these microbial populations perturbs the production of vital bioactive compounds synthesised by the gut microbiome, such as short-chain fatty acids (SCFAs). Of the SCFAs, butyrate is known to be a major source of energy for colonocytes and has valuable effects on the maintenance of intestinal epithelium and blood brain barrier integrity, gut motility and transit, anti-inflammatory effects, and autophagy induction. Inducing endogenous butyrate production is likely to be beneficial for gut-brain homeostasis and for optimal neuronal function. For these reasons, butyrate has gained interest as a potential therapy for not only metabolic and immunological disorders, but also conditions related to the brain, including neurodegenerative diseases. While direct and indirect sources of butyrate, including prebiotics, probiotics, butyrate pro-drugs and glucosidase inhibitors, offer a promising therapeutic avenue, their efficacy and dosage in neurodegenerative conditions remain largely unknown. Here, we review current literature on effects of butyrate relevant to neuronal function, the impact of butyrate in a range of neurodegenerative diseases and related treatments that may have potential for the treatment of neurodegenerative diseases.
Topics: Humans; Neurodegenerative Diseases; Animals; Butyrates; Gastrointestinal Microbiome; Probiotics
PubMed: 38641025
DOI: 10.1016/j.neuint.2024.105745 -
Digestive Diseases and Sciences Apr 1996Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins. Butyrate may be an important... (Review)
Review
Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins. Butyrate may be an important protective agent in colonic carcinogenesis. Trophic effects on normal colonocytes in vitro and in vivo are induced by butyrate. In contrast, butyrate arrests the growth of neoplastic colonocytes and inhibits the preneoplastic hyperproliferation induced by some tumour promoters in vitro. We speculate that selective effects on G-protein activation may explain this paradox of butyrate's effects in normal versus neoplastic colonocytes. Butyrate induces differentiation of colon cancer cell lines. It also regulates the expression of molecules involved in colonocyte growth and adhesion and inhibits the expression of several protooncogenes relevant to colorectal carcinogenesis. Additional studies are needed to evaluate butyrate's antineoplastic effects in vivo and to understand its mechanism(s) of action.
Topics: Animals; Butyrates; Butyric Acid; Colon; Colonic Neoplasms; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Gene Expression Regulation, Neoplastic; Humans; Tumor Cells, Cultured
PubMed: 8674394
DOI: 10.1007/BF02213129 -
Advances in Experimental Medicine and... 1997Butyrate, a SCFA generated by microbial fermentation of dietary substrates, is produced in the colon of humans and may influence colonic disease. It is possible to... (Review)
Review
Butyrate, a SCFA generated by microbial fermentation of dietary substrates, is produced in the colon of humans and may influence colonic disease. It is possible to manipulate the diet in order to enhance levels of butyrate in various regions of the large intestine. Butyrate is absorbed by colonocytes in the proximal colon via passive diffusion and by active transport mechanisms which are linked to various ion exchange transporters. In the distal colon, the main mechanism of absorption is passive diffusion of the lipid-soluble form. Butyrate and other SCFA are important for the absorption of electrolytes by the large intestine and may play a role in preventing certain types of diarrhea. The mechanism by which butyrate and other SCFA exerts control over fluid and electrolyte fluxes in the colon is not well delineated though it may occur through an energy generated fuel effect, the up-regulation of various electrolyte transport systems, as well as possible effects on neuroendocrine factors. Butyrate has been shown to have beneficial effects on some colonic pathologies. This SCFA may be protective against colorectal neoplasia. Butyrate regulates colonic motility, increases colonic blood flow and may enhance colonic anastomosis healing. Butyrate may reduce the symptoms from ulcerative colitis and diversion colitis and it may prevent the progression of colitis in general. Further investigations are needed to confirm these findings in controlled, randomized, double blinded clinical studies.
Topics: Butyrates; Butyric Acid; Colon; Colonic Diseases; Fatty Acids; Humans; Intestinal Absorption; Water-Electrolyte Balance
PubMed: 9361838
DOI: No ID Found -
Scientific Reports May 2019Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Bacterial metabolites and components of the bacterial cell wall are...
Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Bacterial metabolites and components of the bacterial cell wall are likely to provide important links between the intestinal commensal flora and sleep-generating mechanisms in the brain. Butyrate is a short-chain fatty acid produced by the intestinal bacteria by the fermentation of nondigestible polysaccharides. We tested the hypothesis that butyrate may serve as a bacterial-derived sleep-promoting signal. Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%. Both the oral and intraportal administration of butyrate led to a significant drop in body temperature. Systemic subcutaneous or intraperitoneal injection of butyrate did not have any significant effect on sleep or body temperature. The results suggest that the sleep-inducing effects of butyrate are mediated by a sensory mechanism located in the liver and/or in the portal vein wall. Hepatoportal butyrate-sensitive mechanisms may play a role in sleep modulation by the intestinal microbiota.
Topics: Administration, Oral; Animals; Butyrates; Butyric Acid; Gastrointestinal Microbiome; Injections; Mice, Inbred C57BL; Rats, Sprague-Dawley; Sleep; Triglycerides
PubMed: 31065013
DOI: 10.1038/s41598-019-43502-1 -
Journal of Cellular Biochemistry.... 1995Differentiating agents, including butyrate, phenylacetate and several other agents, have long been known to alter abnormal or transformed cell lines in vitro to a more... (Review)
Review
Differentiating agents, including butyrate, phenylacetate and several other agents, have long been known to alter abnormal or transformed cell lines in vitro to a more normal state including phenotype and function. The effect depends on prolonged exposure to a minimum concentration of the agent. In vivo studies of butyrate and analogues have been limited, largely due to rapid in vivo metabolism. A butyrate prodrug, the triglyceride tributyrin, shows great promise in achieving effective and prolonged serum levels when given orally to mice and rats, and has been recommended for human trial. In vitro, butyrate and its mono- and triglyceride have shown potent synergy with retinoic acid, suggesting a ten-fold reduction in serum level requirements. Other butyrate prodrugs have been prepared and studied; several sugar esters of butyrate show promise. Phenylacetate, a normal mammalian metabolite, is also a potent differentiating agent, but its clinical use is limited by its objectionable odor per se and in treated subjects. Phenylbutyrate, a prodrug of phenylacetate, is more acceptable and may have greater promise. The availability of effective prodrugs of effective differentiating agents, such as tributyrin and phenylbutyrate, creates many opportunities for possible therapeutic and chemopreventive applications, especially if synergy in vivo can be demonstrated with retinoids (e.g., retinoic acid) or deltanoids (e.g., active vitamin D analogues), confirming in vitro studies. Particular disease targets would include certain leukemias, thalassemia, and sickle cell anemia.
Topics: Animals; Antimetabolites, Antineoplastic; Butyrates; Butyric Acid; Cell Differentiation; Drug Synergism; Humans; Mice; Phenylacetates; Rats; Triglycerides
PubMed: 8538206
DOI: 10.1002/jcb.240590831 -
Critical Reviews in Food Science and... 2024Brain functions are influenced by the presence, activity, and metabolism of the gut microbiota through the gut-microbiota-brain (GMB) axis. The consumption of a... (Review)
Review
Brain functions are influenced by the presence, activity, and metabolism of the gut microbiota through the gut-microbiota-brain (GMB) axis. The consumption of a fiber-rich diet increases the content of short-chain fatty acids (SCFAs) from bacterial fermentation in the colon. Among SCFAs, butyrate stands out because of its wide array of biological functions, such as ability to influence brain functions. Pharmacologically, sodium butyrate (NaB) regulates gene expression in the brain, where it has several beneficial effects ranging from neurodegenerative diseases to behavioral disorders through inhibitors of histone deacetylases (HDACis). In this context, we review the mechanisms of action of the two types of butyrate on brain functions, with an emphasis on the epigenetic approach. Both types of butyrate are potentially interesting for the prevention and adjuvant therapy of neurological and psychological disorders due to their neuroprotective functions. However, further studies are needed to investigate the possible neuroepigenetic effects of butyrate derived from bacterial fermentation.
Topics: Humans; Brain; Epigenesis, Genetic; Gastrointestinal Microbiome; Butyrates; Fatty Acids, Volatile; Animals; Butyric Acid; Fermentation; Dietary Fiber; Histone Deacetylase Inhibitors; Brain-Gut Axis
PubMed: 36287024
DOI: 10.1080/10408398.2022.2137776 -
European Journal of Cancer Prevention :... Oct 1995
Review
Topics: Animals; Apoptosis; Butyrates; Butyric Acid; Cell Cycle; Cell Differentiation; Cell Division; Colonic Neoplasms; Dietary Fiber; Humans; Intestinal Mucosa; Tumor Cells, Cultured
PubMed: 7496326
DOI: 10.1097/00008469-199510000-00007 -
Journal of Environmental Management May 2022Butyl butyrate (BB) derived from bio-renewable resources is the most promising jet fuel blend. This review highlights essential properties of jet fuel, including... (Review)
Review
Butyl butyrate (BB) derived from bio-renewable resources is the most promising jet fuel blend. This review highlights essential properties of jet fuel, including calorific value, kinematic viscosity, freezing point, flash point, auto-ignition temperature, and density to compare with different bio-renewable chemicals, which are compatible to be blended with the jet fuel. A detailed discussion follows on the importance of intermediate formation, reaction mechanism, and catalyst properties that are critical towards the production of bio-renewable resource-derived BB. BB is primarily produced via the esterification of butyric acid (BA) in butanol (BuOH) with or without using a catalyst. The corresponding reactions are carried out in both homogeneous and heterogeneous phases, provided it has acidic properties. Thus, a wide range of acidic catalysts such as [HSO-pmim] HSO ionic liquids, heteropolyacid, methanesulfonic acid, Dowex 50 Wx8-400 resins, and sulfonated char causes up to 98%, 97.9%, 93.2%, 95.3%, and 90% of BB yield, respectively are critically reviewed. Moreover, reaction mechanism, product, and by-product formation that primarily dictate the BB yield and selectivity have been comprehensively reviewed. In addition, catalytic and mechanistic insights on BB production from other bio-renewable resources such as butyric anhydride, butyraldehyde, dibutyl ether, and methanol have been discussed in this review.
Topics: Biofuels; Butanols; Butyrates; Esterification
PubMed: 35228167
DOI: 10.1016/j.jenvman.2022.114772